The incident occurred on the A684 between Northallerton and the A19 in the area of Winton and involved a white Toyota Aygo and a silver / grey Ford Mondeo.
Sadly, the driver of the Toyota, a woman in her later forties, was pronounced dead at the scene.
The driver of the Ford was taken to hospital and the extent of his injuries is not yet clear.
The road was closed for several hours to enable emergency services to work at the scene. The road re-opened at 2.30pm.
Police are urging anyone who witnessed the collision, saw the vehicles prior to it happening, or has any dashcam footage that could help the investigation, to get in touch.
Please call North Yorkshire Police on 101, select option 2 and ask for Adam Elliott. You can also email email@example.com
Please quote incident number 12190037857 when passing on any information.
North Yorkshire Police is not yet in a position to release the identity of the woman who died.